Expression And Significance Of Nerve Growth Factor Receptor TrkA In Human Laryngocarcinoma

Objective: Laryngeal squamous carcinoma continues to be one of the most common malignant tumors of the head and neck.The incidence of laryngeal cancer is relatively low compared with that of carcinomas of all sites, comprising about 2 % to of all cancers.The dysplasia of laryngeal epidermis is usually graded mild, moderate and severe, depending on the degree of these changes.The laryngeal invasive carcinoma is usually graded well, moderate and poorly differentiated. Although grading of cellular differentiation does not correlate strongly as an independent variable with regard to outcome in most series, more poorly differentiated tumors have a greater likelihood of lymphatic metastasis. Hence,grading of differentiation play an important role in the treatment plan.Recurrence and metastasis are often the primary cause of the high mortality probability of laryngeal carcinoma.Lymph nodal metastasis,which plays a crucial role in prognosis, is often the initial and independent prognostic factor. The Lymph nodal metastasis process contains of many molecules and genes. For example, cell adhesion molecule, cytokine, lymphatic vessel generated related and genetumor metastasis related gene, etc. Therefore, prediction and diagnosis of the cervical lymph nodal metastasis is also very important for the patient's prognosis and treatment plan.TrkA, a trans- membrane tyrosine kinase of 140 kDa with a cytoplasmic tyrosine kinase domain, is a high-affinity nerve growth factor receptor (NGFR). The binding of NGF to TrkA, the high-affinity NGF receptor, results in TrkA phosphorylation that will in turn lead to a scaffolding role for TrkA and recruitment of several adapter proteins and enzymes that ultimately propagate the NGF signal. The NGF- TrkA ligand-receptor pair is thought to have a critical role in the regulation of cell survival, proliferation, and differentiation in neural cells and some malignant tumors. But the expression of the nerve growth factor receptor TrkA in the laryngeal squamous carcinoma has not been reported.Therefore,we investigated the expression of TrkA in human normal vocal cord mucosa,laryngeal papillomas,laryngeal squamous carcinoma and adjacent mucosa tissues and its clinical implications using immuneohistochemistry and the expression of TrkA in Hep-2 cells using immunocytochemistry.Material and Methods:43 cases surgically resected laryngeal carcinoma, which come from department of otorhino- laryngology head and neck surgery, Bethune International Peace Hospital were used. The patients had received neither chemotherapy nor radiation therapy before tumor resection. 13 cases of para-cancer laryngeal mucosa tissues,7 cases of laryngeal papilloma tissues and 12 cases of normal vocal cord mucosa tissues were also recruited.Laryngeal squamous carcinoma cell line (Hep-2 cells), was gifted from the Institute for Cancer Research of America.Using immuneohistochemical , we investigated the expression of TrkA in human laryngeal carcinoma , para-cancer laryngeal mucosa tissues, laryngeal papilloma tissues and normal vocal cord mucosa tissues. Using immunocyto- chemistry,we investigated the positive expression of TrkA in Hep-2 cells.Result:1 The TrkA expression in tissues of laryngeal carcinoma was significantly higher than in para-cancer laryngeal mucosa. There is very remarkable difference between the two groups,χ~2 =4.285(P=0.038).2 The TrkA expression in tissues of laryngeal carcinoma was significantly higher than in tissues of normal vocal cord mucosa tissues. There is very remarkable difference between the two groups,χ~2 =19.08(P<0.001)3 Positive expression of TrkA was detected in all of 43 cases of laryngeal carcinoma tissues. The strong positive expression ratio of TrkA was much higher in moderately and poorly differentiated laryngeal carcinoma group than in well differentiated group. There is very remarkable difference between the two groups,χ~2 =5.581(P=0.018). 4 The strong positive expression ratio of TrkA was much higher in laryngeal carcinoma group with cervical lymph node metastasis than in none lymph node metastasis group.There is very remarkable difference between the two groups,χ~2 =10.518,(P=0.001).5 The trkA protein was also observed in the cytoplasm and nucleus of Hep-2 cells .There are small subsets cells with stronger expression of TrkA, which show larger nucleus or in nucleus cleavaging stage.Conclusions:1 The TrkA expression in tissues of laryngeal carcinoma was significantly higher than in para-cancer laryngeal mucosa.2 The TrkA expression in tissues of laryngeal carcinoma was significantly higher than in tissues of normal vocal cord mucosa tissues.3 The expression of TrkA was much higher in moderately and poorly differentiated laryngeal carcinoma group than in well differentiated group.4 The expression of TrkA was much higher in laryngeal carcinoma group with cervical lymph node metastasis than in none lymph node metastasis group.5 The trkA protein was observed in the subsets of cells with stronger expression of TrkA, which show larger nucleus or in nucleus cleavaging stage. This may provide us a new way to diagnose and treat laryngocarcinoma.